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H Snieder

Publications and source records attributed to H Snieder.

49 records · Page 3Linked to original sources
PubMed1999

Association between birth weight and adult blood pressure in twins: historical cohort study.

OBJECTIVES: To evaluate the associations in twins between within pair differences in birth weight and subsequent blood pressures as adults thereby removing the impact of potential parental confounding variables. DESIGN: Historical cohort study. SETTING: St Thomas's UK adult twin register, June 1992 to September 1995. PARTICIPANTS: 492 pairs of female twins (mean age 54 years). MAIN OUTCOME MEASURES: Mean within pair differences in adult blood pressure in each of four strata of within pair differences in birth weight (0, 1-500 g, 501-1000 g, >1000 g). Differences in blood pressure were analysed before and after adjustment for potential confounders between adult twins, after exclusion of those twin pairs including at least one twin taking antihypertensive drugs, and by zygosity. RESULTS: Reported mean birth weights of heavier and lighter twins were 2.51 (SD 0.61) v 2.12 (0.59) kg respectively. A graded inverse relation between strata of within pair differences in birth weight and differences in adult blood pressure was apparent, with an adjusted blood pressure range of 8.7/5.1 mm Hg across the four strata (test for trend: systolic, P=0.05; diastolic, P=0.09). After excluding those women taking antihypertensive drugs the significance of the association was similar (systolic, P=0.04; diastolic, P=0.10). When differences in blood pressure were stratified for zygosity similar but non-significant trends were apparent. CONCLUSION: It would seem that birth weight is inversely associated with adult blood pressure and that this association is independent of parental confounding variables probably including, in view of the findings in monozygotic twins, genetic factors. The observed blood pressure differences are likely to result from retarded intrauterine growth due to placental dysfunction rather than inadequate maternal nutrition.

Adult↗
PubMed1999

Bivariate genetic analysis of fasting insulin and glucose levels.

The main aim of this study was to estimate the relative influence of genes and environment on fasting insulin levels, which were considered a proxy of insulin resistance. Possible sex differences in genetic and environmental influences, and the origin of the covariance between fasting insulin and glucose were investigated. Subjects were 209 pairs of middle-aged twins, divided into 5 sex-by-zygosity groups. A general bivariate model and a reciprocal causation model including fasting insulin and glucose were used in the analyses. For both quantitative genetic models, a model specifying additive genetic and unique environmental factors, which were the same in males and females, showed the best fit to the data. Heritability estimates were modest and highly similar in both models: 20-25% of the variance in fasting insulin, and around 50% of the variance in fasting glucose levels could be attributed to genetic factors. The two models could not be discriminated on the basis of their fit to the data. A submodel of the general bivariate model suggested that the covariance between glucose and insulin has a unique environmental basis, whereas for the reciprocal causation model both causal paths were needed to explain the phenotypic correlation between insulin and glucose and estimates of the reciprocal paths were of opposite sign, an indication for the expected negative feedback loop.

Adult↗
PubMed1999

Genetic control of the circulating concentration of transforming growth factor type beta1.

The concentration of transforming growth factor beta (TGF-beta) in plasma has been correlated with the development of several diseases, including atherosclerosis and certain forms of cancer. However, the mechanisms that control the concentration of TGF-beta in plasma are poorly understood. In a study of 170 pairs of female twins (average age 57.7 years) we show that the concentration of active plus acid-activatable latent TGF-beta1 [(a+l) TGF-beta therefore is predominantly under genetic control (heritability estimate 0.54). Single strand conformation polymorphism (SSCP) mapping of the TGF-beta1 gene promoter has identified two single base substitution polymorphisms. The two polymorphisms (G-->A at position -800 bp and C-->T at position -509 bp) are in linkage disequilibrium (correlation coefficient Delta = 0.215, P < 0.01). The C-509T polymorphism is significantly associated with the plasma concentration of (a+l) TGF-beta1, explaining 8.2% of the additive genetic variance of (a+l) TGF-beta1 concentration. It is therefore possible that predisposition to atherosclerosis, bone diseases or various forms of cancer may be correlated with the presence of particular alleles at the TGFB1 locus.

Adult↗
PubMed1999

Dissecting the genetic architecture of lipids, lipoproteins, and apolipoproteins: lessons from twin studies.

We review the ways in which twin studies have been used to investigate the genetic architecture of lipids, lipoproteins, and apolipoproteins. We focus on the age dependency of genetic effects and the importance of pleiotropy for the lipid system. Finally, consequences are discussed of age dependency and pleiotropy for the design and power of twin studies aimed at detecting the actual quantitative trait loci (QTLs) involved. It is concluded that twin studies have played an important role and will remain highly valuable for the elucidation of the genetic architecture of lipids, lipoproteins, and apolipoproteins. Twins can efficiently be used to identify the location and function of QTLs. Taking account of pleiotropy and age-dependent gene expression in study design and data analysis will improve the power and efficiency to find these QTLs for components of the lipid system.

Apolipoproteins↗
PubMed1998

Gender-related association between the -93T-->G/D9N haplotype of the lipoprotein lipase gene and elevated lipid levels in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a frequent cause of premature coronary artery disease. Affected family members are characterized by different combinations of elevated cholesterol and/or triglyceride levels. A reduction in lipoprotein lipase (LPL) activity has been observed in a subgroup of FCHL patients. Recently, we have demonstrated an increased frequency of mutations in the LPL gene in Dutch FCHL patients compared to normolipidemic controls. In the present study, we have applied a pedigree-based maximum likelihood method to study the effect of LPL mutations on the phenotypic expression of FCHL in families. In 40 FCHL probandi, three different previously reported mutations in the LPL gene were identified resulting in amino acid changes, D9N, N291S, and S447X. The D9N mutation in exon 2 appeared to be in strong linkage disequilibrium with a T-->G substitution at position -93 in the promoter region of the LPL gene. We present data that the -93T-->G/D9N haplotype is associated with significantly higher levels of LDL and VLDL cholesterol, and VLDL triglycerides. Interestingly, the effect was only observed in male carriers. In line with our previous observations, these results further sustain that the LPL gene is a susceptibility gene for dyslipidemia which explains part of the variability in the phenotype observed among FCHL family members.

Adult↗
PubMed1998

Serum lipids and cardiovascular reactivity to stress.

Several studies have reported an association between serum lipid levels and cardiovascular reactivity to laboratory stressors. Their findings, however, are equivocal. The inconsistencies may be due to shortcomings such as the small number of subjects, the inclusion of patient groups, no control for medication, and no control for age effects. Two studies are presented investigating the relationship in large groups of adolescent and middle-aged males and females. Cholesterol, triglycerides and HDL were measured. Subjects were exposed to mental stressors, and in one study also to a cold pressor test. In addition to heart rate and blood pressure, in one study impedance cardiography was used to measure pre-ejection period, stroke volume and total peripheral resistance. Canonical correlation analysis suggested an association between triglycerides and decreased cardiac reactivity to mental stressors in middle-aged females. Trends in the same direction were found in both middle-aged males and females with respect to reactivity to the cold pressor. These associations, however, were not confirmed when the extreme deciles of the triglyceride distributions were compared with respect to stress reactivity. The fact that associations were completely absent in youngsters but sometimes showed up in older persons suggested an age dependency of the association. In post hoc analyses, indeed, some evidence was found for stronger cardiac responsivity being associated with cholesterol specifically in relatively older males. In females, in contrast to this, the association between triglycerides and cardiac responsivity was stronger in the younger group. More detailed measurement techniques, of specifically vascular processes, may be needed to explore further the effects of sex and age on the association between lipids and stress reactivity.

Adolescent↗
PubMed1998

Genes control the cessation of a woman's reproductive life: a twin study of hysterectomy and age at menopause.

A classical twin study was performed to assess the extent to which genetic factors explain individual differences in age at menopause and (indications for) hysterectomy. It was further examined whether a genetic effect on the timing of the menopause was mediated through a genetic effect on age at menarche. The subjects were 275 monozygotic and 353 dizygotic female twin pairs. Maximum likelihood model fitting was used to estimate genetic and environmental variance components, Kaplan-Meier survival analysis was used to account for censored data, and the Cox proportional hazards model was used to adjust for potential confounders. A model specifying additive genetic and unique environmental factors showed the best fit to the data, yielding a heritability (h2) for age at menopause of 63%. The significance of the genetic effect was confirmed by the survival analysis and was not affected by adjustment for confounders. Both early and late menopause were found to be significantly influenced by genetic factors. Hysterectomy also showed considerable heritability (h2 = 59%), as did its two main indications: fibroids (h2 = 69%) and menorrhagia (h2 = 55%). The genetic contribution to the variance in age at menarche was estimated to be 45%, with the majority (37%) being due to dominant genetic effects. No correlation was found between age at menopause and age at menarche, suggesting different genetic mechanisms. This study provides convincing evidence for the importance of genetic factors in determining natural and surgical menopause. Understanding how genes control the timing of menopause and exploring whether these genes are indirectly associated with disease are important areas for future study.

Age Factors↗
PubMed1998

Heritability of blood pressure increases during mental stress.

We studied the influence of mental stress on the contributions of genes and environment to individual variation in systolic (SBP) and diastolic (DBP) blood pressure by structural equation modelling in 320 adolescent male and female twins. Blood pressure data were collected during rest and during a reaction time and a mental arithmetic task. Univariate analyses of SBP and DBP showed familial aggregation for blood pressure. A genetic explanation for this resemblance was most likely, although during rest conditions a model that attributed familial resemblance to shared environmental factors, also fitted the data. There was no evidence for sex differences in heritabilities. Multivariate analyses showed significant heterogeneity between sexes for the intercorrelations of the blood pressure data measured under different rest and task conditions. Multivariate genetic analyses were therefore carried out separately in males and females. For SBP and DBP in females and for SBP in males an increase in heritabilities was seen for blood pressure measured during stress, as compared to rest measurements. The influence of shared environmental factors decreased during stress. For DBP in males no significant contributions of shared environment were found. The multivariate analyses indicated that the same genetic and environmental influences are expressed during rest and stress conditions.

Adolescent↗
PubMed1997

Genetics and behavioral medicine: risk factors for cardiovascular disease.

This is the second in a series of three articles addressing the intersection of interests in behavioral genetics and behavioral medicine. In this article, we use risk factors for cardiovascular disease as a prototypical trait for which behavioral genetic approaches provide powerful tools for understanding how risk factors, behavior, and health outcomes are related. The approach synthesizes a number of methods and areas of interest in an attempt to arrive at a comprehensive, whole-organism understanding of health-related risk factors and their response to behavioral interventions.

Adolescent↗
PubMed1997

Heritability of respiratory sinus arrhythmia: dependency on task and respiration rate.

In this study, we investigated the genetic and environmental origin of individual differences in respiratory sinus arrhythmia (RSA) during rest and during four stress tasks. We used a multivariate model including age, RSA, and respiration rate. Participants were 208 male and female pairs of middle-aged twins. A model without sex differences, specifying additive genetic and unique environmental factors, showed the best fit across all conditions. Heritability of RSA ranged from 28% to 43%. Correction for respiration rate yielded RSA heritabilities of similar size. The covariance between respiration rate and RSA was best explained by a combination of correlated unique environmental and correlated additive genetic factors. Combined with data from an earlier project, RSA from 317 adolescent and 712 middle-aged individuals of both sexes was available. This large data set showed that (a) sex differences in mean RSA are absent and (b) RSA decreases considerably from adolescence (111.5 ms) to middle age (60.0 ms).

Adolescent↗
PubMed1997

The age dependency of gene expression for plasma lipids, lipoproteins, and apolipoproteins.

The aim of this study was to investigate and disentangle the genetic and nongenetic causes of stability and change in lipids and (apo)lipoproteins that occur during the lifespan. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) were measured in a group of 160 middle-aged parents and their twin offspring (first project) and in a group of 203 middle-aged twin pairs (second project). Combining the data of both projects enabled the estimation of the extent to which measured lipid parameters are influenced by different genes in adolescence and adulthood. To that end, an extended quantitative genetic model was specified, which allowed the estimation of heritabilities for each sex and generation separately. Heritabilities were similar for both sexes and both generations. Larger variances in the parental generation could be ascribed to proportional increases in both unique environmental and additive genetic variance from childhood to adulthood, which led to similar heritability estimates in adolescent and middle-aged twins. Although the magnitudes of heritabilities were similar across generations, results showed that, for total cholesterol, triglycerides, HDL, and LDL, partly different genes are expressed in adolescence compared to adulthood. For triglycerides, only 46% of the genetic variance was common to both age groups; for total cholesterol this was 80%. Intermediate values were found for HDL (66%) and LDL (76%). For ApoA1, ApoB, and Lp(a), the same genes seem to act in both generations.

Adolescent↗
PubMedDate not supplied

Sleep disordered breathing in pediatric patients with tetralogy of Fallot.

Adverse effects on the pulmonary circulation in obstructive sleep disordered breathing (SDB) may place children with heart lesions affecting the right ventricle at increased risk for morbidity and mortality. We examined the distribution and effects of SDB in pediatric patients with tetralogy of Fallot (TOF). Families of 37 pediatric patients with TOF completed a survey of cardiac symptoms and school performance as well as a Pediatric Sleep Questionnaire (PSQ), a validated questionnaire for the screening of SDB in children 2-18 years of age. Medical records were reviewed for growth parameters, medical history, and most recent electrocardiogram (ECG) findings. Data from patients with SDB (PSQ score > or = 8, n = 14) were compared to data from patients without SDB (PSQ score < 8; n = 23). The prevalence of SDB in this population (38%) was significantly higher than the published prevalence of 5% in a healthy general pediatric population (p < 0.001). No significant difference was found in age, gender, or age and sex standardized body mass index between patients with or without SDB. No difference was seen in medication use or timing of surgical repair, whether primary or palliative. Patients with SDB had a significantly higher cardiac symptom score (p = 0.01) and increasing PSQ scores correlated with worsening cardiac symptom scores (p = 0.006). Increasing PSQ scores also correlated with worsening school performance (p = 0.001). No differences were seen in ECG data. The screened prevalence of SDB in the pediatric population with TOF is higher than in the general population; patients with TOF and SDB are more likely to have worse cardiac symptoms and poor school performance.

Adolescent↗